Ossifying fibromyxoid tumor of soft parts: A clinicopathologic, proteomic, and genomic study

Rondell Graham, Sarah Dry, Xinmin Li, Scott Binder, Armita Bahrami, Susana C. Raimondi, Ahmet Dogan, Subhankar Chakraborty, Joshua J. Souchek, Andrew L. Folpe

Research output: Contribution to journalArticle

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Abstract

Ossifying fibromyxoid tumor (OFMTs) of soft parts is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. To better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescence in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were conducted on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 men and 17 women (median age, 52 y; range 39 to 63 y) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9), and trunk (N=5). Median tumor size was 5.4 cm (range, 1.0 to 21.0 cm). Cases were classified as typical OFMT (26 of 46, 57%), atypical OFMT (5 of 46, 11%), and malignant OFMT (15 of 46 cases, 32%). Clinical follow-up (27 cases, median 55 months' duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were as follows: S-100 protein (30 of 41, 73%), desmin (15 of 39, 38%), cytokeratin (4 of 35, 11%), EMA (5 of 32, 16%), SMA (2 of 34, 6%), INI-1 (lost in mosaic pattern in 14 of 19, 74%), EAAT4 (31 of 39, 80%), MUC4 (3 of 14, 21%), NFP (8 of 10, 80%) and CD56 (6 of 14, 43%). Gene expression profiling showed typical and malignant OFMTs to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S-100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5 of 7 (71%) cases. We conclude that malignant OFMTs exist and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a "scrambled" phenotype in OFMTs. Loss of INI-1 or other genes on 22q is likely important in the pathogenesis of these rare tumors.

Original languageEnglish (US)
Pages (from-to)1615-1625
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume35
Issue number11
DOIs
StatePublished - Nov 2011

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Proteomics
Neoplasms
Excitatory Amino Acid Transporter 4
S100 Proteins
Fluorescence In Situ Hybridization
Neurofilament Proteins
Mucin-1
Desmin
Gene Expression Profiling
Paraffin
Formaldehyde
Smooth Muscle
Actins
Keratin-4
Neurons
Schwann Cells
Keratins
Natural History
Cartilage

Keywords

  • fluorescence in situ hybridization
  • gene expression profiling
  • immunohistochemistry
  • INI-1
  • ossifying fibromyxoid tumor of soft parts
  • proteomics

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Ossifying fibromyxoid tumor of soft parts : A clinicopathologic, proteomic, and genomic study. / Graham, Rondell; Dry, Sarah; Li, Xinmin; Binder, Scott; Bahrami, Armita; Raimondi, Susana C.; Dogan, Ahmet; Chakraborty, Subhankar; Souchek, Joshua J.; Folpe, Andrew L.

In: American Journal of Surgical Pathology, Vol. 35, No. 11, 11.2011, p. 1615-1625.

Research output: Contribution to journalArticle

Graham, R, Dry, S, Li, X, Binder, S, Bahrami, A, Raimondi, SC, Dogan, A, Chakraborty, S, Souchek, JJ & Folpe, AL 2011, 'Ossifying fibromyxoid tumor of soft parts: A clinicopathologic, proteomic, and genomic study', American Journal of Surgical Pathology, vol. 35, no. 11, pp. 1615-1625. https://doi.org/10.1097/PAS.0b013e3182284a3f
Graham, Rondell ; Dry, Sarah ; Li, Xinmin ; Binder, Scott ; Bahrami, Armita ; Raimondi, Susana C. ; Dogan, Ahmet ; Chakraborty, Subhankar ; Souchek, Joshua J. ; Folpe, Andrew L. / Ossifying fibromyxoid tumor of soft parts : A clinicopathologic, proteomic, and genomic study. In: American Journal of Surgical Pathology. 2011 ; Vol. 35, No. 11. pp. 1615-1625.
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abstract = "Ossifying fibromyxoid tumor (OFMTs) of soft parts is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. To better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescence in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were conducted on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 men and 17 women (median age, 52 y; range 39 to 63 y) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9), and trunk (N=5). Median tumor size was 5.4 cm (range, 1.0 to 21.0 cm). Cases were classified as typical OFMT (26 of 46, 57{\%}), atypical OFMT (5 of 46, 11{\%}), and malignant OFMT (15 of 46 cases, 32{\%}). Clinical follow-up (27 cases, median 55 months' duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were as follows: S-100 protein (30 of 41, 73{\%}), desmin (15 of 39, 38{\%}), cytokeratin (4 of 35, 11{\%}), EMA (5 of 32, 16{\%}), SMA (2 of 34, 6{\%}), INI-1 (lost in mosaic pattern in 14 of 19, 74{\%}), EAAT4 (31 of 39, 80{\%}), MUC4 (3 of 14, 21{\%}), NFP (8 of 10, 80{\%}) and CD56 (6 of 14, 43{\%}). Gene expression profiling showed typical and malignant OFMTs to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S-100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5 of 7 (71{\%}) cases. We conclude that malignant OFMTs exist and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a {"}scrambled{"} phenotype in OFMTs. Loss of INI-1 or other genes on 22q is likely important in the pathogenesis of these rare tumors.",
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T1 - Ossifying fibromyxoid tumor of soft parts

T2 - A clinicopathologic, proteomic, and genomic study

AU - Graham, Rondell

AU - Dry, Sarah

AU - Li, Xinmin

AU - Binder, Scott

AU - Bahrami, Armita

AU - Raimondi, Susana C.

AU - Dogan, Ahmet

AU - Chakraborty, Subhankar

AU - Souchek, Joshua J.

AU - Folpe, Andrew L.

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N2 - Ossifying fibromyxoid tumor (OFMTs) of soft parts is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. To better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescence in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were conducted on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 men and 17 women (median age, 52 y; range 39 to 63 y) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9), and trunk (N=5). Median tumor size was 5.4 cm (range, 1.0 to 21.0 cm). Cases were classified as typical OFMT (26 of 46, 57%), atypical OFMT (5 of 46, 11%), and malignant OFMT (15 of 46 cases, 32%). Clinical follow-up (27 cases, median 55 months' duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were as follows: S-100 protein (30 of 41, 73%), desmin (15 of 39, 38%), cytokeratin (4 of 35, 11%), EMA (5 of 32, 16%), SMA (2 of 34, 6%), INI-1 (lost in mosaic pattern in 14 of 19, 74%), EAAT4 (31 of 39, 80%), MUC4 (3 of 14, 21%), NFP (8 of 10, 80%) and CD56 (6 of 14, 43%). Gene expression profiling showed typical and malignant OFMTs to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S-100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5 of 7 (71%) cases. We conclude that malignant OFMTs exist and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a "scrambled" phenotype in OFMTs. Loss of INI-1 or other genes on 22q is likely important in the pathogenesis of these rare tumors.

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KW - gene expression profiling

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KW - proteomics

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